Aryl- and heteroaryl-substituted ureas have been described as inhibitors of cytokine production and effective therapeutics in cytokine-mediated diseases including inflammatory and autoimmune diseases. Examples of such compounds are reported in U.S. Pat. Nos. 6,080,763 and 6,319,921, and WO 00/55139 including aryl- or heteroaryl-substituted ureas of the formula shown below: 
Among the favored Ar1 are substituted or unsubstituted aryl or heteroaryl groups, including those defined below in this application.
A preferred step in the synthesis of this class of compounds is the formation of a urea bond as illustrated in Scheme I. 
In Scheme I, Z can be an isocyanate or isothiocyanate or an amine (in which case the isocyanate or isothiocyanate is formed in situ) or Z can be RbOC(O)NH where ORb is a leaving group. The reaction may also be carried out in the reverse sense (i.e., Ar1-Z+H2N—Ar-L-Q).
U.S. application Ser. No. 09/611,109 discloses a method of making similar compounds by reacting a carbamate, made from reaction of a Ar1—NH2 and a haloformate, and the appropriate the amine as shown below to form the product compound: 
The methods previously described for the synthesis of (I) require the preparation of intermediate (II), where Ar1 is the desired aryl or heteroaryl group. Preparation of (II) often requires a multi-step synthesis. For example the preferred intermediate (IIa) shown below is prepared by reaction of an aryl hydrazine with a ketonitrile. See also U.S. application Ser. Nos. 09/698,442, 09/902,085 and 09/735,160. Often, preferred aryl hydrazines and ketonitriles are not available commercially and must themselves be synthesized. This non-convergent approach also makes it inconvenient and tedious to prepare a series of analogs of formula (I) differing only in R3: 
Recent reports in the chemical literature described improved methods for the coupling of aryl groups to NH-containing heterocycles. For example, P. Y. S. Lam et al. (Tetrahedron Letters, 1998, 2941) describes the coupling of aryl groups to NH-containing heterocycles in the presence of cupric acetate and base. The reaction occurs under mild conditions and is not air-sensitive. The reaction is successful with a variety of aryl boronic acids, many of which are commercially available.
In the novel process disclosed herein, R3 is coupled to intermediate (Ia) in a final step. 
Intermediates required for the final coupling step of R3 to Ia are often commercially available or readily prepared.